Treatment

There are many approaches to tackle Uveal Melanoma. Sophie Piperno-Neumann from Institut Curie in Paris discusses UM treatment and the challenge to treat metastatic UM.

Treatment

General Approach

Treatments for uveal cancer most often are surgery, radiation therapy, or both. When planning treatment a clinician will take into consideration the following aspects:

The size of the tumour and its location in the eye;

How far it has grown or spread – the stage of the tumour;

How much is it affecting the patient's sight;

The pathology report (when available);

General health and fitness.

There are several concerns when treating uveal melanoma, including the preservation of sight. As with many types of cancer, the earlier the diagnosis is made, the easier it is to cure or manage it.

If the tumour is large or has already impaired the patient's sight, surgery may be needed to remove the eye. This surgery is called enucleation. Previously, treatment consisted of this sole possibility. Nowadays, this has been superseded whenever possible by conservative eye-preserving therapies that include various forms of radiation therapy, laser treatment and local tumour resection.

Great concern must also be given to the prevention/treatment of spreading of the tumour to other parts of the body. A positive outcome with the initial treatment of the tumour is very important, however it does not mean the cancer has not spread. Uveal melanoma spreads through the blood vessels and there is no way of testing for this at the present time other than assessing risk with genetic examination of the primary (eye) tumour cells and checking for changes elsewhere in the body, namely the liver.

Treatment for uveal melanomas that have spread outside the eye

The tumour can spread locally to extra ocular structures such as:

The optic nerve;

The eye socket;

If the tumour has spread, enucleation may be needed to remove the affected eye and the surrounding tissues as well as radiation therapy in some cases.

The tumour can spread to other regions of the body distant from the eye. The most common place for this is the liver. Since metastatic uveal melanoma is rare, it is hard to implement clinical trials to find the best treatment. In this case patients are often prescribed chemotherapy, immunotherapy, or a combination of treatments.

Treatment for recurrent eye melanoma

If uveal melanoma has come back after treatment, the most likely approach will be enucleation. After surgery, radiation therapy may also be needed.

If the tumour has come back in the tissues around the eyeball (extraocular melanoma) or has spread to another part of the body such as the liver (metastatic uveal melanoma), one may need to undergo chemotherapy, immunotherapy, or both. UM CURE 2020 research findings should contribute to structure clinical trials to test how novel treatments can help cure this condition.

Managing Metastatic Uveal Melanoma

In a great number of patients with uveal melanoma, metastatic disease is not detected at diagnosis. Up to 50% of patients develop metastatic disease at any time from the initial UM diagnosis to several decades later. The liver may be the only metastatic site even though lung, bone and skin metastases can also form. Brain metastases are extremely rare. Metastatic uveal melanoma requires the expertise of different specialists. A multi-disciplinary approach in a reference centre specialized in cancer and liver disease should be available. The rarity of this cancer supports the recommendation that an experienced specialist team treat metastatic uveal cancer patients. This is not a mandatory approach and people can choose to be treated nearer home.

In a specialised centre, patients often undergo a variety of scans. The liver would likely be scanned with contrast-enhanced MRI with diffusion weighting. Chest, pelvis and abdomen scanned with CT or PET CT. In addition, one may have a bone scan if bone pain is present. Brain scans are not always recommended if there are no symptoms.

If the metastatic disease has only liver involvement with a few areas affected within it, surgical resection is often the most suitable treatment. Before the procedure, patients will likely have an exploratory laparoscopy (surgical procedure) to check that resection of the metastasis is possible. If the patient is not able to have a resection, the specialist team should consider other treatments directly to the liver. If the cancer is outside of the liver, or has also spread to other organs, the patient may be a candidate for chemotherapy.

The current UM national guidelines in the UK (NICE accredited, see link) state that in some cases, patients may be suitable candidates to immunotherapy. It still remains uncertain how effective these treatments are for uveal melanoma. Recent research has suggested that there is a distinct group of metastatic UM patients that respond to immunotherapy. These patients seem to have tumours that elicit a better immune response than previously thought. Finally, patients should be informed about available clinical trials appropriate for them.

Surveillance/Follow up

Since there are controversial results about the different methods available for screening for the appearance of metastatic disease, patients should have an individual plan decided in collaboration with their clinicians. Patients should be informed about the benefits and limitations of a tumour biopsy at this point.

If the tumour is removed from the eye (surgical treatment) or if the patient has a biopsy taken, additional information can be obtained from the tumour tissue to assert:

The type of tumour cells present;

The cell cycle and division activity of the tumour cells;

The genetic profile of the tumour cells;

The importance of a tumour biopsy is the identification of a high-risk group allowing for determination of liver scan frequencies. The gathering of all clinical information with the auxiliary diagnostic scans and furthermore the genetic profile of the tumour (obtained through the biopsy tissue) is crucial for overall risk assessment. Patients should also be offered the decision as to how much information they would like to receive, as the decision of whether to find out if they are at high risk of cancer spreading can be very difficult.

Patients that are considered high risk with respect to developing secondary tumours in the liver should be offered a follow-up with a clinical review, scans with liver-specific imaging by a non-ionizing modality and a consultant for follow-up support. Continued CT scans of the liver should not be performed and blood tests alone are inadequate.

There is currently discussion on whether clear evidence exists to demonstrate if surveillance after treatment for uveal melanoma metastases is useful. However, it seems reasonable to perform cross-sectional imaging soon after a surgical or non-surgical liver procedure (4-6 weeks) to assess treatment response. Moreover it is recommended by the UK national guidelines (NICE accredited) that the same imaging modality is used for assessment and follow up; contrast-enhanced MRI with DWI is currently thought to be the optimal choice.